Hypothermia after cardiac arrest: Beneficial, but slow to be adopted

The standard of care

In view of the available clinical data, the 2002 ILCOR guidelines and a 2005 statement from the American Heart Association advocated mild therapeutic hypothermia for survivors of out-of-hospital ventricular tachycardia or fibrillation.¹⁶ Subsequently, this therapy has become more widely practiced and accepted as the standard of care among critical-care providers.

Of note, some public health officials and local governments are strongly promoting this treatment for survivors of cardiac arrest in the community.¹⁷ More and more of these groups are mandating that these patients be transported only to hospitals that have therapeutic hypothermia protocols in place, bypassing those not equipped to provide this treatment.¹⁸

INDICATIONS, CONTRAINDICATIONS, AND GRAY AREAS

What are the indications and contraindications to the use of hypothermia after out-of-hospital cardiac arrest? What are some of the “gray areas”?

Indications. This treatment is indicated for comatose adults who have had a witnessed cardiac arrest, whose initial cardiac rhythm was ventricular fibrillation or pulseless ventricular tachycardia, and whose circulation spontaneously returned in less than 60 minutes with basic and advanced cardiac life support. This carries a class I recommendation, level of evidence B, and was recently reinforced in the 2010 update to the American Heart Association guidelines for cardiopulmonary resuscitation.¹⁹

Absolute contraindications include hemorrhagic stroke (which must be proved by computed tomography) and cardiac arrest due to trauma (Table 2). Other major contraindications are a Glasgow Coma Scale score of 8 or higher before the initiation of mild therapeutic hypothermia, cardiac arrest due to drug overdose, and preexisting hypothermia (< 34°C) when first-responders arrive.

Relative contraindications include baseline coagulopathy and severe hypotension (mean atrial pressure < 60 mm Hg) that is not correctable by fluid infusion, vasopressors, or invasive hemodynamic support.

Gray areas. There are not enough data to make a firm recommendation about whether to apply mild therapeutic hypothermia if a witnessed cardiac arrest with ventricular fibrillation or ventricular tachycardia occurs in the hospital, but data from out-of-hospital cardiac arrest patients appear applicable for hospitalized patients.

The data are also quite limited and equivocal on its use for out-of-hospital cardiac arrest in patients whose initial cardiac rhythm is pulseless electrical activity or asystole,^20,21 likely because of the competing risk of comorbidities and the resultant lower baseline survival rate in these patients.

Consequently, for in-hospital postarrest patients with any initial rhythm and for out-of-hospital cardiac arrest patients with rhythms other than ventricular tachycardia or ventricular fibrillation, the 2010 guideline recommendation on the use of mild therapeutic hypothermia is less enthusiastic (class IIb, level of evidence B).¹⁹

There are also few data on the use of mild therapeutic hypothermia in post-arrest patients in circulatory shock requiring vasopressors or intra-aortic balloon counterpulsation, largely limited to case series and comparisons with historical controls.^22,23 Further investigation is clearly needed in these areas. Until then, it should be considered at the physician’s and the team’s discretion, on a case-by-case basis.

HYPOTHERMIA IN CASES OF VENTRICULAR FIBRILLATION AND ACUTE CORONARY SYNDROME

The value of coronary angiography after out-of-hospital cardiac arrest was first highlighted by Spaulding et al,²⁴ who performed it urgently in 84 consecutive survivors of out-of-hospital cardiac arrest, 36 of whom had ST-segment elevation myocardial infarction (STEMI). Angiography uncovered an acute coronary occlusion in 40 (48%) of the 84 patients.

In this series, ST-segment elevation was a strong predictor of acute coronary occlusion (odds ratio 4.3; 95% CI 1.6–2.0; P = .004). However, 9 patients without chest pain or ST elevation were also found to have an occluded infarct-related artery. Successful angioplasty was an independent predictor of survival, highlighting the importance of an angiographic definition in this population.

These findings were recently confirmed in the larger Parisian Region Out of Hospital Cardiac Arrest (PROCAT) registry in 435 patients who had no obvious extracardiac cause of arrest, for whom successful culprit coronary angioplasty was associated with survival.²⁵

Angioplasty comes first, but neither treatment need be delayed

Efforts to induce hypothermia must not be allowed to delay the door-to-balloon time of post-arrest patients in the setting of STEMI. The top priority is establishing patency of the infarct-related artery with a goal of salvaging ischemic myocardium and obtaining mechanical and electrical stabilization.

Fortunately, mild therapeutic hypothermia does not necessarily delay emergency revascularization if hypothermia protocols are well established. In fact, induction of mild therapeutic hypothermia prior to or on arrival at the catheterization laboratory has been shown to be feasible and safe.^26,27

We believe that all centers performing primary percutaneous coronary intervention for STEMI should have immediate access to and expertise in mild therapeutic hypothermia. Regional planning and integration of STEMI and out-of-hospital cardiac arrest networks will ensure that most patients with STEMI have access to this treatment when it is indicated.

Does hypothermia help the heart? Does it increase bleeding?

Researchers have been interested in therapeutic hypothermia as a means of reducing myocardial infarct size,^28,29 but clinical trials have not shown a clear-cut benefit in this regard. However, these investigations have also added to the evidence that antiplatelet and anticoagulation therapy in patients undergoing mild therapeutic hypothermia does not result in a statistically significant excess of major bleeding events, which is a potential concern.

Of note, these studies were neither powered nor specifically designed to evaluate for major bleeding as an end point. Therefore, these complications should still be carefully monitored for.